[Study on anti-HIV-1 activities of composite extract from salvia yunnanensis].
OBJECTIVE
To explore and evaluate the activities of composite extract from Salvia Yunnanensis and in cell cultures (DS-MEF) for inhibition of human immuno-deficiency virus type 1 (HIV-1) in vitro and in cell cultures.


METHODS
The inhibitory activity of DS-MEF on HIV-1 reverse transcriptase (RT), protease (PR) and integrase (IN) were detected in vitro with radionuclide 3H incorporation, fluorescence assay and enzyme-linked immunosorbent assay respectively. The human T-lymphocyte MT-4 cell line, human T-lymphocyte H 9 cell line chronically infected with HIV-1 IIIB, and the fresh peripheral blood mononuclear cell (PBMC) of healthy persons as well as the laboratory passed HIV-1 IIIB and the clinically isolated HIV-1 AZT sensitive 018a or resistant 018c infected cell cultures were used for evaluating the cytotoxicities and inhibitory activities of DS-MEF on HIV-1 P 24 antigen. The acute toxicities of DS-MEF on KM mice were determined by gastric gavages and intraperitoneal injections with various dosages.


RESULTS
The IC50 of DS-MEF for inhibiting HIV-1 IN, RT and PR were 2.59 +/- 0.50 mg/L, 27.39 +/- 11.18 mg/L and 9.38 +/- 2.45 mg/L respectively. In MT-4 cell cultures infected with HIV-1 III, TC50 were 13.19 +/- 6.07 mg/L, IC50 and SI of anti-HIV-1 activity were 0.224 +/- 0.163 mg/L and 58.7; in chronically infected H 9 cell cultures, TC50 were 18.11 +/- 9.84 mg/L, IC50 on HIV-1 P 24 antigen and SI were l7.230 +/- 21.114 mg/L and 1.1 respectively; TC50 in HIV-1 infected PBMC cultures were 288.70 +/- 0.08 mg/L; IC50 on AZT sensitive HIV-1 018a: 26.42 +/- 11.16 mg/L, and SI: 10.9; On AZT resistant HIV-1 018c, IC50: 27.87 +/-5.35 mg/L, and SI: 10.4. Moreover, DS-MEF showed synergistic effect with AZT or nevirapine (NVP) on HIV-1 IIIB in MT-4 cell cultures, the respective combination index was 0.78 or 0.67. DS-MEF showed no acute toxicity in KM mice with the dosage up to 20 g/kg via gastrogavage, and the 50% lethal dose (LD50) via intraperitoneal injection was 1.18 g/kg.


CONCLUSIONS
DS-MEF is a promising anti- HIV-1 agent with low toxicity in mice and possesses multi-targets and effective activities.
Peng
Zong-gen
ZG
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peiking Union Medical College, Beijing 100050.
Qin
De-hua
DH
Teng
Li
L
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001892:Camphanes; D002460:Cell Line; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053723:Panax notoginseng; D027544:Salvia / Q000737:chemistry*; D027561:Salvia miltiorrhiza; D013601:T-Lymphocytes / Q000821:virology; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D001892:Camphanes; D004365:Drugs, Chinese Herbal; D014764:Viral Proteins; C000604051:danshen dripping pill